The present invention relates to pharmaceutical formulations containing ibuprofen and methods for producing the same. More particularly, the present invention involves a method for preparing improved ibuprofen granulations.
It has been recognized that solid dosage forms such as tablets containing ibuprofen and other ingredients tend to exhibit stability problems, including the formation of low melting point eutectics. In general, eutectic compositions often exhibit unique physical properties such as melting or freezing points which are not characteristic of the individual constituents. For example, eutectic compositions composed of two constituents having different melting points may have melting point which is lower than either of the constituents. In some cases, the unique physical properties of a eutectic composition are desirable. For example, eutectic compositions of two or more metals are frequently used in low melting point solders in order to incorporate the strength or some other property of one metal with a desirable quality found in a second metal.
Alternatively, the physical properties exhibited by some eutectic compositions can be undesirable. In particular, certain pharmaceutical formulations can form eutectic compositions which exhibit undesirable melting point depressions. It is recognized in the art that these melting point depressions may significantly impair the stability of the formulation. In some cases, eutectic compositions occur immediately upon intimate association of the constituents present in a formulation. Alternatively, some formulations develop a eutectic character after the constituents have been in intimate contact with one another for a prolonged period of time. Other formulations develop a eutectic character after having undergone exposure to certain environmental conditions, such as fluctuations in temperature, pressure or humidity.
In particular, it has been found that certain ibuprofen-containing solid dosage forms such as powders, granules, pellets, capsules, tablets and the like exhibit stability problems. It is further recognized that the instability of such dosage forms is at least in part attributable to the tendency of these formulations to undergo undesirable melting point depressions. For example, although the melting point of ibuprofen is approximately 75.degree. C., formulations containing ibuprofen and terfenadine melt at temperatures ranging from about 50.degree. to about 75.degree. C. This melting point depression phenomena is thought to be attributable to the tendency of ibuprofen to form eutectic compositions with certain substances. Ibuprofen also forms low melting point eutectics with substances such as diphenhydramine hydrochloride and astemizole.
Eutectic formations, however, significantly reduce the shelf-life of ibuprofen-containing products. For example, many prior art tablets containing ibuprofen and other active ingredients and/or excipients tend to exhibit structural deteriorations such as crumbling, pitting and fissuring, as well as a loss of color as a result of the eutectic formation. Alterations in the crystalline structures. have also been observed.
Some ibuprofen-containing formulations tend to exhibit melting point depressions almost immediately. Other formulations are stable initially but undergo changes in consistency upon exposure to fluctuations in temperature and/or other environmental factors. Still other ibuprofen-containing formulations may inherently develop these melting point depressions upon prolonged intimate contact of the ibuprofen with the other constituents present in the formulations. Each of these situations create storage problems. Consequently, there is a need to develop methods for preparing stable ibuprofen-containing formulations.
It is therefore an object of the present invention to provide new methods of preparing ibuprofen granulations.
It is also an object of the present invention to provide an improved method for preparing solid dosage forms containing ibuprofen in combination with other ingredients.